Methods of forming Poly(ester amide)-based drug delivery systems with controlled release rate and morphology

• US 8,377,499 B2
• Filed: 02/28/2011
• Issued: 02/19/2013
• Est. Priority Date: 02/28/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Kleiner, Lothar Walter, Pacetti, Stephen Dirk, Hossainy, Syed Faiyaz Ahmed, Trollsas, O. Mikael, Ngo, Michael Huy, DesNoyer, Jessica Renee
• Primary Examiner(s): Yuan, Dah-Wei
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US13/037,166
• Publication Number:
  US 20110151104A1
• Time in Patent Office: 722 Days
• Field of Search: 623/1.38, 514/449, 523/113, 604/500, 427/2.12, 427/2.13, 427/2.31, 430/66, 424/423
• US Class Current: 427/2.1
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A method of forming a coating on a medical device having a controlled morphology is described.

Claims

1. A method for forming a coating on a medical device comprising:

providing a coating composition comprising a polymer and a solvent of the polymer,

applying the coating composition onto the medical device,

inducing phase inversion in the coating composition by the addition of a non-solvent of the polymer to the composition, and

causing the coating composition to form a layer of coating on the medical device,

wherein the coating has a controlled morphology for controlling the release of an agent and/or a drug from the coating;

wherein the polymer comprises a poly(ester amide) polymer; and

wherein the poly(ester amide) polymer is PEA-TEMPO, PEA-Benzyl, a poly(ester amide) polymer of 0.5 L-Leucine (cyclohexanediol) 0.5 L-Leucine (hexanediol) sebacinate and/or a poly(ester amide) polymer of L-Phenyl Alanine (propanediol) sebacinate.

2. The method of claim 1, wherein the coating composition applied to the medical device further comprises a second non-solvent of the polymer.

3. The method of claim 2, wherein the non-solvent added and/or the second non-solvent is a bioactive agent.

4. The method of claim 1, wherein subsequent to the phase inversion, evaporation of the solvent occurs.

5. The method of claim 1, wherein the non-solvent added is water and the addition of the water induces phase inversion.

6. The method of claim 5, wherein the water is introduced into the applied coating composition by condensation or absorption of water into the applied coating composition.

7. The method of claim 2, wherein the layer of the coating comprises a two-phase morphology.

8. The method of claim 7, wherein the morphology comprises a non-solvent rich phase.

9. The method of claim 8, wherein the non-solvent rich phase is isolated or interconnected.

10. The method of claim 9, wherein

isolated non-solvent rich phase means that the phase comprises isolated non-solvent pockets, and

interconnected non-solvent rich phase means that the phase comprises a honeycomb-type or a finger-type structure.

11. The method of claim 1, wherein the coating composition further comprises a surfactant.

12. The method of claim 11, wherein the surfactant is selected from the group consisting of poly(ethylene oxide)-polypropylene oxide)-poly(ethylene oxide) surfactants, tetra-functional block copolymers based on ethylene oxide and propylene oxide, Polysorbate surfactants, Sorbitan based surfactants, Polyoxyethylene based surfactants, trisiloxane based surfactants, Poloxamer surfactants, and combinations thereof.

13. The method of claim 1, wherein the polymer has a glass transition temperature above ambient temperature.

14. The method of claim 13, wherein the polymer has a glass transition temperature above about 37°

C.

15. The method of claim 1, wherein the coating has a rough or coarse morphology or the coating has a two-phase morphology with channels or pores.

16. The method of claim 2, wherein the non-solvent added and/or the second non-solvent is a drug.

17. The method of claim 16, wherein the drug is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus, tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

18. The method of claim 1, wherein the coating composition further comprises a drug soluble in the polymer.

19. The method of claim 1, wherein phase inversion is induced by extraction of the solvent from the composition with the non-solvent for the polymer, and optionally, where the non-solvent is a supercritical fluid.

20. The method of claim 11, wherein the surfactant is sorbitan Monostearate, and/or polyoxyethylene (20) Oleyl ether.

21. The method of claim 1, wherein the poly(ester amide) polymer is a poly(ester amide) polymide of 0.5 L-Leucine (cyclohexanediol) 0.5 L-Leucine (hexanediol) sebacinate;

and

wherein the solvent comprises a solvent selected from the group consisting of Methanol, Ethanol, n-Propanol, Isopropanol, 1-Butanol, dimethyl acetamide, tetrahydrifuran, dimethyl formamide, Dichloromethane, dimethyl sulfoxide, Chloroform, Trichloroethane, Tetrachloroethane, Trichloroethylene, and combinations thereof.

22. The method of claim 21, wherein the non-solvent comprises a substance selected from the group consisting of water, Dioxane, Cyclohexanone, methyl ethyl ketone, Benzene, Toluene, Xylene, Pentane, Hexane, Heptane, Octane, Cyclohexane, Acetone, and combinations thereof.

23. The method of claim 1, wherein the poly(ester amide) polymer is poly(ester amide) polymer of 0.5 L-Leucine (Cyclohexanediol) 0.5 L-Leucine (hexanediol) sebacinate;

and

wherein the solvent is selected from the group consisting of Methanol, Ethanol, n-Propanol, Isopropanol, 1-Butanol, dimethyl acetamide, tetrahydrofuran, dimethyl formamide, Dichloromethane, dimethyl sulfoxide, Chloroform, Trichloroethane, Tetrachloroethane, Trichloroethylene, and combinations thereof.

24. The method of claim 23, wherein the non-solvent is selected from the group consisting of water, Dioxane, Cyclohexanone, methyl ethyl ketone, Benzene, Toluene, Xylene, Pentane, Hexane, Heptane, Octane, Cyclohexane, Acetone, and combinations thereof.

25. The method of claim 1, wherein the poly(ester amide) polymer is a poly(ester amide) polymer of L-Phenyl Alanine (propanediol) sebacinate;

wherein the solvent is selected from the group consisting of dimethyl acetamide, tetrahydrofuran, dimethyl formamide, Dichloromethane, dimethyl sulfoxide, Chloroform, Trichloroethane, Tetrachloroethane, Trichloroethylene, and combinations thereof; and

wherein the non-solvent is selected from the group consisting of Water, Dioxane, Cyclohexanone, methyl ethyl ketone, Benzene, Toluene, Xylene, Pentane, Hexane, Heptane, Octane, Cyclohexane, Acetone, Methanol, Ethanol, n-Propanol, Isopropanol, 1-Butanol, and combinations thereof.